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Comparison of Endothelial Biomarkers According to Reversibility of Pulmonary Hypertension Secondary to Congenital Heart Disease

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Abstract

The reversibility of pulmonary arterial hypertension (PAH) in children with congenital heart disease (CHD) is strongly associated with the degree of intimal proliferation, vessel narrowing, and number of circulating endothelial cells (CECs). Circulating endothelial cells may arise from either endothelial damage or accelerated turnover during vessel remodeling, but nothing is known about endothelial microparticles (EMPs) and other biomarkers reflecting endothelial alterations. This study aimed to document endothelial markers further according to the irreversibility of PAH secondary to CHD. The study investigated soluble markers of endothelial damage or activation (thrombomodulin, soluble endothelial protein C receptor, and soluble E-selectin), inflammation (interleukin-6), and angiogenic cytokine levels [vascular endothelial growth factor (VEGF) and placental growth factor (PlGF)] in 26 patients with CHD, 16 with reversible PAH (median age, 2 years) and 10 with irreversible PAH (median age, 9 years). Endothelial activation/apoptosis was evaluated by measuring EMP levels. Plasma procoagulant activity also was measured. The results show that the levels of soluble markers indicating endothelial activation were not predictors of PAH irreversibility. Lower levels of PlGF were observed in reversible compared with irreversible PAH but were not associated with the CEC level, the mean pulmonary artery pressure (mPAP), or age. No significant difference in procoagulant activity or EMP level was found between irreversible and reversible PAH. Among a large panel of biomarkers reflecting endothelial activation, regeneration, and injury, the high CEC levels previously described proved to be the only marker allowing discrimination between reversible and irreversible PAH secondary to CHD.

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Acknowledgments

We thank Isabelle Zezepanski for her technical assistance. This work was supported by research grants from the Leducq TransAtlantic Network of Excellence on Atherothrombosis Research (Grant 04CVD01), Fondation de France, Leg Poix (Paris, France), and ARCFA (Association pour la recherche en cardiologie du foetus à l’adulte). Laetitia Mauge received grants from AP-HP. Sophie Gandrille was supported by APHP/INSERM contrat d’interface.

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Authors and Affiliations

  1. Université Paris Descartes, Paris, France

    David M. Smadja, Pascale Gaussem, Laetitia Mauge, Sophie Gandrille, Damien Bonnet & Marilyne Lévy

  2. Faculté de Pharmacie, INSERM Unité 765, Paris, France

    David M. Smadja, Pascale Gaussem, Laetitia Mauge & Sophie Gandrille

  3. AP-HP, Hôpital Européen Georges Pompidou, 20 rue Leblanc, 75015, Paris, France

    David M. Smadja, Pascale Gaussem, Laetitia Mauge, Sophie Gandrille, Véronique Remones & Séverine Peyrard

  4. UPRES EA4068, UFR Biomédicale des Saints Pères, Paris, France

    Marilyne Lévy

  5. Faculté de Pharmacie et Hôpital de la Conception, INSERM Unité 608, Marseille, France

    Romaric Lacroix & Florence Sabatier

  6. Centre d’Investigation Épidémiologique 4, INSERM, Paris, France

    Séverine Peyrard

  7. AP-HP, Hôpital Necker-Enfants Malades, Paris, France

    Damien Bonnet & Marilyne Lévy

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  1. David M. Smadja
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  2. Pascale Gaussem
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  10. Marilyne Lévy
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Correspondence to David M. Smadja.

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Smadja, D.M., Gaussem, P., Mauge, L. et al. Comparison of Endothelial Biomarkers According to Reversibility of Pulmonary Hypertension Secondary to Congenital Heart Disease. Pediatr Cardiol 31, 657–662 (2010). https://doi.org/10.1007/s00246-010-9674-0

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  • DOI: https://doi.org/10.1007/s00246-010-9674-0

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